The objectives of this research are to determine the chemical factors that regulate the transition of proliferative skin epithelial cells into non-proliferative cells, and to define the basis for this activity at the molecular level. A small molecular weight substance, the Connective Tissue Factor (CTF) increases the replicative time of skin epithelial cells in vitro and has been partially purified from adult rabbit skin. Further purification will be carried out using ion exchange chromatography. The role of CTF in human skin diseases characterized by increased numbers of proliferative cells will be examined. Micromethods to measure the content of CTF in 3 mm biopsies of human skin will be developed, and the level of CTF in involved and in uninvolved skin of subjects with psoriasis will be developed, and the levels of CTF in involved and in uninvolved skin of subjects with psoriasis will be determined. The mechanism of action of CTF will be studied in vivo and in vitro. Chromatin will be isolated from proliferative and non- proliferative cells, and the composition of histones and non-histone acidic proteins will be analyzed by disc gel electrophoresis. Acidic proteins will be labeled with C14-L-leucine in vivo and in vitro, and the effect of CTF on the synthesis of each acidic protein will be determind. The binding of CTF to acidic protein will be measured. The composition of, and changes in, nucleotide pools during proliferative cell transitions will be determined in the presence and absence of CTF. The above changes in metabolism and their significance in the metabolic regulation of epithelial cell growth will be further tested in guinea pig epithelial cells which do not convert to non-proliferative cells in vitro.